Topical sunscreen compositions are commonly used during outdoor work or leisure as a means for providing protection of exposed skin against acute and chronic adverse effects of solar radiation such as sunburn, cancer and photo-aging. Many effective sunscreen preparations are sold commercially or are described in cosmetic or pharmaceutical literature. In general sunscreen preparations are formulated as creams, lotions or oils containing as the active agent an ultra violet radiation absorbing chemical compound. The sunscreen functions by blocking passage of ultra violet radiation thereby preventing its penetration into the skin.
According to Zecchino et al. (U.S. Pat. No. 5,008,100), sunscreen agents may be characterized in the order of decreasing effectiveness as either highly chromophoric (monomeric organic compounds and inorganic compounds such as titanium dioxide) and minimally chromophoric (polymeric organic solids).
Organic sunscreens are classified into UV-A filters, UV-B filters or broad spectrum filters (UV-A and UV-B functionality in a single molecule) depending on the type of radiation they absorb. UV-A sunscreens absorb radiation in the 320 to 400 nm regions of the ultra violet spectrum and UV-B sunscreens absorb radiation in the 290 to 320 nm regions of the ultra violet spectrum.
Broad band sunscreens (UV-A and UV-B functionality) absorb radiation in the 290 to 400 nm region of the ultra violet spectrum and have two maximums, one in the UV-B region and the other in the UV-A region.
Representative references related to UV sunscreens are:
U.S. Pat. No. 3,278,448, which discloses cinnamic acid derivatives such as 4-hydroxy, 3-5-ditertbutyl-alphacarbethoxy-cinnamic acid ether ester in column 2, line 20;
U.S. Pat. No. 3,538,226, which describes cinnamic acid alkyl ester derivatives at column 1, lines 15-31 and column 2, lines 1-12 and column 3, lines 30-55 and 60;
U.S. Pat. No. 5,175,340, which describes cinnamic acid alkyl esters having hydroxy radicals and alkoxy radicals on the phenyl ring, and
U.S. Pat. No. 5,830,441, which describes UV absorbents containing a cyano or cinnamyl moiety by the generic formula at col. 2, lines 1-21.
Other references which disclose cinnamide compounds include U.S. Pat. Nos. 5,601,811, 4,335,054, 5,124,354, 5,294,643 and 5,514,711.
Unfortunately, some of the highly chromophoric monomeric organic compounds employed in sunscreen compositions are not photostable and the protection from sun damage is lost. In addition to lack of photostability of many organic sunscreens, they do not possess an antioxidant property which is essential for protecting skin or hair.
The ideal sunscreen formulation should be nontoxic and non-irritating to the skin tissue and be capable of convenient application in a uniform continuous film. The product should be chemically and physically stable so as to provide an acceptable shelf life upon storage. It is particularly desirable that the preparation should retain its protective effect over a prolonged period after application. Thus, the active agent when present on the skin must be resistant to chemical and/or photo degradation.
Techniques for stabilizing UV absorbent compositions are known. Representative disclosures in this area include U.S. Pat. Nos. 5,567,418, 5,538,716, 5,951,968 and 5,670,140.
It is desirable to provide the antioxidant and photostable sunscreen functionality in a single molecule to enhance the effectiveness of the antioxidant properties.
There is provided by the present invention compounds with sunscreen activity, i.e. they are chromophoric within the ultra violet radiation range of from 290-400 nm and they also exhibit antioxidant properties. These compounds are represented by general formula I 
In formula I, A is a moiety which provides chromophoric properties within the UV radiation range of 290-400 nm. This moiety comprises one divalent group or two monovalent groups with at least one group having carbonyl (Cxe2x95x90O) functionality. For formula I, each R6 is independently linear or branched C1-C8 alkyl and R5 is hydrogen or R6. The one or more compounds of formula I can preferably stabilize an additional sunscreening agent against photodegradation from exposure to sunlight. Preferred compounds are of formula II below. 
For formula II,
R1 is selected from the group consisting ofxe2x80x94C(O)CH3, xe2x80x94CO2R3, xe2x80x94C(O)NH2, xe2x80x94C(O)N(R4)2, and xe2x80x94CN;
X is O or NH;
R2 is linear or branched C1 to C30 alkyl;
R3 is linear or branched C1 to C20 alkyl;
each R4 is independently hydrogen or linear or branched C1 to C8 alkyl;
R5 is linear or branched C1-C8 alkyl or hydrogen; and
R6 is linear or branched C1-C8 alkyl.
Included within the preferred compounds are those of formula II wherein R1 is linear or branched C1-C4 alkyl, X is oxygen and R2 is linear or branched C1-C12 alkyl. Of these compounds, those more preferred have R1 as C(O)CH3 or CO2R3 wherein R3 is a linear or branched C1 to C4 alkyl. For compounds wherein R1 is C(O)N(R4)2, R4 is preferably hydrogen or a linear or branched C1-C4 alkyl.
While compounds having from C1-C4 alkyl groups for R2 and R3 are preferred, significant utility can be obtained from compounds wherein R2 and R3 are linear or branched C8 to C20 alkyl or C12 to C20 alkyl groups.
Another preferred class of compounds are those of formulae III and IV wherein R1 and R2 are as defined for formula I with R3 being C1-C8 alkyl and R4 being C1-C4 alkyl. 
Examples of compounds consistent with Formulae III or IV include those selected from the group consisting of
ethyl-alpha-cyano-3-methoxy-4-hydroxy cinnamate,
ethyl-alpha-acetyl-3-methoxy-4-hydroxy cinnamate,
iso-propyl-alpha-acetyl-3-methoxy-4-hydroxy cinnamate,
iso-amyl-alpha-acetyl-3-methoxy-4-hydroxy cinnamate,
2-ethylhexyl-alpha-acetyl-3-methoxy-4-hydroxy cinnamate,
diethyl-3-methoxy-4-hydroxy benzylidene malonate,
di-(2-ethylhexyl)-3-methoxy-4-hydroxy benzylidene malonate,
diisoamyl-3-methoxy-4-hydroxy benzylidene malonate,
didodccyl-3-methoxy-4-hydroxy benzylidene malonate,
dipalmitoyl-3-methoxy-4-hydroxy benzylidene malonate, and
di-isopropyl-3-methoxy-4-hydroxy benzylidene malonate.
di-(2-ethyhexyl)-3-methoxy-4-hydroxy-5-isopropyl-benzylidene malonate
di-isoamyl-3-methoxy-4-hydroxy-5-tert.butyl-benzylidene malonate
iso-amyl-alpha-acetyl-3-methoxy-4-hydroxy-5-isopropyl cinnamate
iso-amyl-alpha-acetyl-3-methoxy-4-hydroxy-5-tert.butyl cinnamate
The present invention also provides sunscreen formulations which comprise a compound of formula I, II, III and/or IV. These sunscreen formulations are effective in absorbing illumination in the range of wavelengths of 320 nm and above. Amounts of the compounds of formula I, II, III and/or IV within such compositions typically range from 0.1 to 40 wt % based on the total weight of the sunscreen. These sunscreen formulations can contain one or more additional organic sunscreen agents for filtering UV-B or UV-A rays or they may additionally contain one or more metal oxide sunscreen agents such as titanium dioxide or zinc oxide.
These sunscreen formulations may additionally contain a carrier and at least one component selected from the group consisting of dispersing agents, preservatives, anti-foams, perfumes, oils, waxes, propellants, dyes, pigment emulsifiers, surfactants, thickeners, humectants, exfoliants and emollients. These sunscreen formulations may be in the form of a cosmetic composition with a cosmetically acceptable carrier and one or more cosmetic adjuvants. The sunscreen formulation can optionally have conventional antioxidants or other stabilizers which do not have UV absorbing characteristics.
Methods of using these sunscreen compositions and methods for improving the photostability of sunscreen formulations are also provided. The methods of using the sunscreen formulations comprise applying a sunscreen formulation which contains a compound of formula I, II, III and/or IV to a substrate. Preferred substrates are skin and hair. To improve the photostability of a sunscreen formulation, a compound of formula I, II, III and/or IV is added to the sunscreen formulation in an amount sufficient to reduce the loss of UV absorbance of the sunscreen as it is irradiated. Typical amounts fall within the range of 0.1% to 40 wt %, based on the total weight of said sunscreen formulation. More typically, the amount falls within the range of 1 wt % to 25 wt %. The amount of organic sunscreen compound of formulae I, II, III and/or IV, preferably ranges from about 3 wt % to about 15 wt % of the sunscreen formulation. Other ingredients referred to above and discussed more particularly below are generally used in an amount from about 0.1 wt % to about 10 wt % of the sunscreen formulation. The balance comprises a cosmetically or pharmaceutically acceptable carrier.
The sunscreen formulations of this invention preferably offer protection from UV radiation with wavelengths of about 290 nm to 400 nm and preferably from wavelengths in the range of about 290-370 nm. Sunscreen formulations of this invention also typically have a sunscreening protection factor (SPF) range of from about 2 to 60, with a preferred SPF range of from about 10 to about 45. The target SPF range can be achieved with a combination of both inorganic and organic chromophoric compounds. SPF is determined by techniques well known in the art, on human skin as described in the Federal Register, August 25, 1978, Vol. 43, No. 166, pages 38259-38269 (Sunscreen Drug Products for Over-The-Counter Human Use, Food and Drug Administration). SPF values can also be approximated using in-vitro models as described, for example, in J. Soc. Cosmet. Chem. 44:127-133 (May/June 1989).
The sunscreen formulations may contain dispersing agents, emulsifiers or thickening agents to assist in applying a uniform layer of the active compounds. Suitable dispersing agents for the sunscreen formulations include those useful for dispersing organic or inorganic sunscreen agents in either a water phase, oil phase, or part of an emulsion, including, for example, chitosan.
Emulsifiers may be used in the sunscreen formulations to disperse one or more of the compounds of formulae I, II, III and/or IV or other component of the sunscreen formulation. Suitable emulsifiers include conventional agents such as, for example, glycerol stearate, stearyl alcohol, cetyl alcohol, dimethicone copolyol phosphate, hexadecyl-D-glucoside, octadecyl-D-glucoside, etc.
Thickening agents may be used to increase the viscosity of the sunscreen formulations. Suitable thickening agents include carbomers, acrylate/acrylonitrile copolymers, xanthan gum and combinations of these. The carbomer thickeners include the crosslinked CARBOPOL(copyright) acrylic polymers from B.F. Goodrich. The amount of thickener within the sunscreen formulation, on a solids basis without water, may range from about 0.001 to about 5%, preferably from 0.01 to about 1% and optimally from about 0.1 to about 0.5% by weight.
Minor optional adjunct ingredients for the sunscreen formulations to be applied to skin or hair may include preservatives, waterproofing agents, fragrances, anti-foam agents, plant extracts (Aloe vera, witch hazel, cucumber, etc) opacifiers, skin conditioning agents and colorants, each in amounts effective to accomplish their respective functions.
The sunscreen formulations may optionally contain an ingredient which enhances the waterproof properties such as, compounds that form a polymeric film, such as dimethicone copolyol phosphate, dilsostearoyl trimethyolpropane siloxysilicate, chitosan, dimethicone, polyethylene, polyvinylpyrrolidone (PVP), polyvinylpyrrolidone/vinylacetate, PVP/Eiconsene copolymer and adipic acids/diethylene glycol/glycerine crosspolymer etc. Waterproofing agents may be present at levels of from about 0.01 to about 10% by weight.
The sunscreen formulations may also optionally contain one or more skin conditioning agents. These include humectants, exfoliants and emollients.
Humectants are polyhydric alcohols intended for moisturizing, reducing scaling and stimulating the removal of built scale from the skin. Typically polyhydric alcohols include polyalkylene glycols and more preferably alkylene polyols and their derivatives. Illustrative are propylene glycol, dipropylene glycol, polypropylene glycol, polyethylene glycol, sorbitol, 2-pyrrolidone-5-carboxylate, hydroxypropyl sorbitol, hexylene glycol, ethoxydiglycol 1,3-butylene glycol, 1,2,6-hexanetriol, glycerin, ethoxylated glycerin, propoxylated glycerin and mixtures thereof. Most preferably the humectant is glycerin. Amounts of humectant can range anywhere from 1 to 30%, preferably from 2 to 20% and optimally from about 5 to 10% by weight of the sunscreen composition.
The exfoliants suitable for use in the present may be selected from alpha-hydroxy carboxylic acids, beta hydroxycarboxylic acids and salts of these acids. Most preferred are glycolic, lactic and salicylic acids and their alkali, metal or ammonium salts.
Suitable emollients include those agents known for softening the skin or hair which may be selected from hydrocarbons, fatty acids, fatty alcohols and esters. Petrolatum is a common hydrocarbon type of emollient conditioning agent. Other hydrocarbons that may be employed include alkyl benzoate, mineral oil, polyolefins such as polydecene, and paraffins, such as isohexadecane. Fatty acids and alcohols typically have from about 10 to 30 carbon atoms. Illustrative are myristic, isostearic, hydroxystearic, oleic, linoleic, ricinoleic, behenic and eruicic acids and alcohols. Oily ester emollients may be those selected from one or more of the following, triglyceride esters, acetoglyceride esters, ethoxylated glycerides, alkyl esters of fatty acids, ether esters, polyhydric alcohol esters and wax esters. Additional emollients or hydrophobic agents include C12 to C15 alkyl benzoate, dioctyladipate, octyl stearate, octyldodecanol, hexyl laurate, octyldodecyl neopentanoate, cyclomethicone, dicapryl ether, dimethicone, phenyl trimethicone, isopropyl myristate, capriylic/capric glycerides, propylene glycol dicaprylate/dicaprate and decyl oleate.
The sunscreen formulations may optionally contain one or more inorganic sunscreen agents as discussed above including micro fine surface treated titanium dioxide and micro fine untreated and surface treated zinc oxide. Titanium dioxide in the sunscreen compositions preferably has a mean primary particle size of between 5 and 150 nm and preferably from 10 to 100 nm. Titanium dioxide may have anatase, rutile or amorphous structure. The zinc oxide in the sunscreen compositions preferably has a mean primary particle size of between 5 nm and 150 nm, preferably between 10 nm and 100 nm. Examples of modified titanium dioxide compositions include:
Eusolex(copyright) T-45D (surface treated with alumina and simethicone, 45% dispersion in isononoyl isononoate);
Eusolex(copyright)T-Aqua, (surface treated with aluminum hydroxide, 25% dispersion in water); and
Eusolex(copyright) T-2000 (surface treated with alumina and simethicone), all available from MERCK KGaA.
The sunscreen formulation may also contain one or more additional monomeric organic chromophoric compounds. These can either be UV-A, UV-B or broad band filters. Examples of suitable UV-A sunscreens include benzophenone derivatives, menthyl anthranilate, butyl methoxydibenzoyl methane and benzylidene-dioxoimidazoline derivatives. Examples of suitable UV-B sunscreens include cinnamate derivatives, salicylate derivatives, para-aminobenzoic acid derivatives, camphor derivatives, phenylbenzimidazole derivatives and diphenylacrylate derivatives. Examples of suitable broad-band sunscreen include benzotriazole derivatives and triazine derivatives such as anisotriazone. Others include ethylhexyltriazone and diethylhexylbutamidotriazone.
Particularly useful organic sunscreen agents that can be introduced are Avobenzone, 2-ethylhexyl p-methoxycinnamate, 4,4xe2x80x2-t-butylmethoxydibenzoyl methane, 2 hydroxy-4-methoxybenzophenone, octyldimethyl p-aminobenzoic acid, 2,2-dihydroxy-4-methoxybenzophenone, ethyl-4-[bis(hydroxypropyl)]aminobenzoate, 2-ethylhexyl-2-cyano-3,3-diphenylacrylate, 2-ethylhexylsalicylate, glycerol p-aminobenzoate, 3,3,5-trimethylcyclohexylsal icylate, methylanthrani late, p-dimethylaminobenzoic acid, 2-ethylhexyl p-dimethylaminobenzoate, 2-phenylbenzimidazole-5-5-sulfonic acid, 2-(p-dimethylamino phenyl-5-sulfoniobenzoxazoic acid and mixtures thereof.
Examples of useful commercially available organic sunscreen agents that can be introduced include 2-phenylbenzimidazole-5-sulphonic acid, 2-(4-methylbenzylidene)-camphor, 4-isopropyldibenzoyl methane all of the Eusolex(trademark) series sold by EM Industries and Merck KGaA, Darmstadt, Germany.
Although not preferred, the sunscreen formulation may contain an additional antioxidant. Examples of suitable antioxidants which provide stability include p-hydroxybenzoic acid and its derivatives (ethylisobutyl, glyceryl esters of p-hydroxybenzoic acid); salicylates (octylamyl, phenyl, benzyl menthyl, glycerol and dipropyleneglycol esters); cumarin derivatives; flavones; hydroxy or methoxy substituted benzophenones; uric or tannic acid and its derivatives; hydroquinone; and benzophenones.
In addition to providing sunscreen activity at levels which provide U.V. absorption, the compounds of Formula I can be introduced into a skin care formulation, a hair care formulation or other personal care formulations such as cosmetic formulations at levels which provide antioxidant activity. These compounds can be used with or without conventional antioxidants in personal care formulations such as hair care, skin care and cosmetic formulations.
The personal care formulations can be in the form of creams, ointments, suspensions, powders, oil, lotions, oleo alcoholic lotions, fatty gels, oleo-alcoholic gels and lotions, solid sticks, foams, emulsions, liquid dispersions, sprays and aerosols. More specific forms include: lipsticks, foundations, makeup, loose or press powder, eye blush, eye shadow and nail lacquer.
Sunscreen formulations of this invention as described in Formulations 1-9 can be prepared by conventional means.
Procedure:
Combine phase B ingredients. Stir and heat to 70-75xc2x0 C. Combine Phase A ingredients. Heat while stirring to 70-75xc2x0 C. Add Phase B to Phase A while stirring. Add preservative. Stir, allowing mixture to cool to room temperature.
Procedure
Combine A-1; stir and heat to 60xc2x0 C. until all solids are dissolved. Disperse A-2 in A-1 with agitation. Combine B-1; stir and heat to 60xc2x0 C. Disperse B-2 in B-1 with agitation. Add A to B while stirring vigorously. Gently homogenize allowing mixture to cool to 40xc2x0 C. Add C to A/B: gently homogenize until mixture is uniform. Stir with anchor mixer allowing mixture to reach 25xc2x0 C. prior to packaging. Use a high shear pump spray device for dispensing (e.g., Eurogel pump by Seaquist Perfect)
Procedure
Add Phase A ingredients to main vessel under impeller agitation. Heat phase A to 75-80xc2x0 C. Combine Phase B ingredients; heat and mix to 85xc2x0 C. Slowly add Phase B to batch; mix for 15 minutes at 85xc2x0 C. Remove from heat; switch to paddle mixing and cool to room temperature.
Procedure
Combine A-1; stir and heat to 55-60xc2x0 C. until all solids are dissolved. Disperse A-1 in A-1 by propeller agitation. Combine B; stir and heat to 50-55xc2x0 C. Slowly add B to A while stirring vigorously. Add C to A/B; gently homogenize until mixture is uniform. Stir with anchor mixer allowing mixture to cool to room temperature.
Procedure
Combine A-1; heat to 50xc2x0 C. while stirring until methylparaben is dissolved. Disperse A-2 in A-1 with a sifter. Heat A to 65xc2x0 C. Combine B: heat to 65-70xc2x0 C. while stirring until solids are dissolved. Add B to A. Homogenize Add C at 55-60xc2x0 C. Continue to homogenize allowing mixture to cool to 40-45xc2x0 C. Add D; stir with propeller mixer until uniform. Adjust pH with TEA to 6.5-7.0
Procedure
Prepare Phase B by dispersing Carbopol in water. Heat the dispersion to 70-75xc2x0 C. Combine Phase A ingredients. Stir and heat to 70-75xc2x0 C. Add Phase B to Phase A while stirring. Add Phase C. Homogenize until mixture cools to 45-40xc2x0 C. Add Phase D. Stir allowing mixture to cool to room temperature.
Procedure
Preapare Phase B by dispersing Carbopol in water. Heat the dispersion to 70-75xc2x0 C. Combine Phase A ingredients. Stir and heat to 70-75xc2x0 C. Add Phase B to Phase A while stirring. Add Phase C. Homogenize until mixture cools to 45-40xc2x0 C. Add Phase D. Stir allowing mixture to cool to room temperature.
Procedure
Preapare Phase B by dispersing Carbopol in water. Heat the dispersion to 70-75xc2x0 C. Combine Phase A ingredients. Stir and heat to 70-75xc2x0 C. Add Phase B to Phase A while stirring. Add Phase C. Homogenize until mixture cools to 45-40xc2x0 C. Add Phase D. Stir allowing mixture to cool to room temperature.
Procedure
Preapare Phase B by dispersing Carbopol in water. Heat the dispersion to 70-75xc2x0 C. Combine Phase A ingredients. Stir and heat to 70-75xc2x0 C. Add Phase B to Phase A while stirring. Add Phase C. Homogenize until mixture cools to 45-40xc2x0 C. Add Phase D. Stir allowing mixture to cool to room temperature.
Methods of preparation of two compounds of the invention are illustrated below. 
The resultant sunscreens have been found to have an SPF of approximately 14.
The entire disclosure of all applications, patents and publications, cited above are hereby incorporated by reference.